Pawde Anuya*, Patil Devendra**, Khadkikar Rashmi***,
****. Chauhan AR
(* Senior Registrar, ** Second Year Resident, *** Assistant Professor, **** Additional Professor. Department of Obstetrics and Gynecology,
College and K.E.M
Hospital, .) Mumbai, India
Hereditary bleeding disorders are an important cause of puberty menorrhagia and the consequences can be life threatening. A twelve year old girl, known case of Factor V and VIII deficiency, presented to a tertiary care centre at menarche with menorrhagia. She was successfully managed with transfusions of cryoprecipitate, fresh frozen plasma (FFP) and Factor VIII concentrate along with oral progesterone. She is now on oral contraceptive pills. This case is presented as combined factor deficiency is a rarity. Early diagnosis, consultation with hematologist and appropriate treatment are essential.
Puberty menorrhagia is defined as bleeding of more than 80 ml/cycle or for more than 7 days. Most common cause of puberty menorrhagia is immature hypothalamo-pituitary-ovarian axis. Other causes include hereditary bleeding disorders, hypothyroidism, and anovulatory cycles due to polycystic ovarian disease. Hemophilia, though not very common, is an important cause for puberty menorrhagia and can be life threatening. It usually presents with excess bleeding at menarche with mid-cycle abdominal pain. History of repeated excess bleeding from gums or wounds along with family history of similar complaints may be corroborative. [1,2]
Miss RRG 12 year old girl presented with history of attainment of menarche 3 days ago with excessive vaginal bleeding, with use of 6-7 large pads per day. Bleeding was not associated with pain in abdomen or any other complaints. She was a diagnosed case of Factor V and Factor VIII deficiency since the last 8 years, and gave history of multiple blood transfusions, fresh frozen plasma and cryoprecipitate transfusions in the past. There was no history suggestive of thyroid disorder or tuberculosis. Family history was significant; her younger brother aged 8 was diagnosed in infancy as a case of Factor VIII deficiency after multiple bleeding episodes and her father, though asymptomatic, is also Factor VIII deficient.
On examination the patient was stable, with mild pallor. There was no evidence of petechiae or bruising. Thyroid, breast and systemic examinations were unremarkable. Abdomen was soft and non-tender. On local examination bleeding with clots was seen. Per rectal examination revealed small uterus.
On investigations, hemoglobin was 8.8 g%, platelet count was normal. Significant abnormality was seen in coagulation profile with abnormal prothrombin time (PT 19.4 against control of 8.9), activated partial thomboplastin time (APTT 87.1 vs 28.0 control) and International Normalised Ratio (INR) of 2.18. Ultrasonography revealed normal uterus and ovaries.
In consultation with hematologist, patient was transfused 3 units of cryoprecipitate and 2 units of fresh frozen plasma daily along with oral tranexamic acid thrice daily. However, despite this, the bleeding continued in the same amount for next 3 days. Hence oral medroxyprogesterone acetate was added in the dose of 5mg thrice daily. Oral iron and folic acid supplementation was given for correction of anemia. Bleeding did not respond completely to treatment, hence Factor VIII concentrate in the dose of 50IU/kg was transfused; bleeding stopped on day 8 of treatment. Subsequently, she was started on oral contraceptive pills, was counseled and discharged.
Bleeding disorders should be suspected in patients with puberty menorrhagia with history of repeated gum bleeding, delayed wound healing, easy bruising, epistaxis, bleeding from tooth extraction, repeated blood transfusions and family history. Commonly seen disorders are hemophilia A and B (deficiency of factor VIII and IX respectively), von Willebrand disease, factor V deficiency, Glanzmann’s thrombasthenia, and idiopathic thrombocytopenia. Though combined deficiencies as seen in our case are known to occur, they are rare and have severe consequences.
Combined factor V and VIII deficiency is a rare autosomal recessive disorder with incidence of 1 in 1,000,000 cases, caused by a single gene defect in chromosome 18.[3,4] In extremely rare cases (1 in 10 billion) factor V and factor VIII could be inherited separately instead of a single gene defect.
Treatment modalities used to control bleeding are tranexamic acid, progesterone alone or oral contraceptive pills, though often bleeding may not respond to these drugs alone. Factor V deficiency can only be treated by FFP in the dose of 15-20ml/kg. FFP is also rich in factor VIII; however FFP alone may be insufficient to treat Factor VIII deficiency and additional treatment with factor VIII concentrate may be required. This concentrate may be plasma derived or recombinant factor VIII, in the dose of 20-50IU/kg as per requirement.  Other drug that has been used for factor VIII deficiency is desmopressin.
Hereditary bleeding disorders should be suspected in all cases of puberty menorrhagia. Detailed personal and family history may guide to the diagnosis and appropriate treatment may prevent life threatening consequences.
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2. Mikhail S, Varadarajan R, Kouides P. The prevalence of haemostasis in adolescents with menorrhagia referred to a haemophilia treatment centre. Hemophilia 2007; 13: 627-632.
3. Kenneth Kaushansky. Inherited deficiencies of coagulation factor II, V, VIII, X, XI, XIII, combined deficiency of Factor V and VIII and of Vitamin K- dependant factors. Kenneth Kaushansky, Ernest Beutler, Marshall A Lichtman. Williams Hematology. 8th edition.
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McGraw- Hill Companies, Inc. China
4. Spreafico M, Peyvani F. Combined FV and FVIII deficiency. Hemophilia 2008;14:1201-1208.
5. Fogarty PF, Kessler CM. Hemophilia A and B. In Kitchens C, Kessler C, Konkle B, editors. Consultative Hemostasis and Thrombosis; 3rd ed. Elsevier. 2013; pp 50-53.
Pawde A, Patil D, Khadkikar R,
Puberty Menorrhagia Due To Combined Factor V
And Viii Deficiency. JPGO 2014 Volume 1 Number 4 Available from: http://www.jpgo.org/2014/04/puberty-menorrhagia-due-to-combined.html Chauhan AR.